Analysis and Screening of Cell Secretion Profiles

1. A system for discretely resolving analytes associated with a cellular population comprising: a plurality of sample retention regions that receive at least one cell distributed from a population of cells and retain an associated plurality of analytes released by the at least one cell; a plurality of analyte detection regions patterned with a plurality of discretely positioned analyte detection moieties, the analyte detection regions disposed along parallel lines forming a barcode pattern alignable with the sample retention regions whereby, upon coupling, released analytes selectively associate with the plurality of analyte detection moieties forming an analyte barcode pattern for each analyte detection region; a plurality of first alignment markers disposed about the plurality of sample retention regions and a plurality of second alignment markers disposed about the plurality of analyte detection regions; an imaging apparatus that generates a plurality of images for selected sample retention regions and retained at least one cell and additionally at least one first alignment marker, the imaging apparatus further generating a plurality of images for analyte detection regions corresponding to the selected sample regions and associated analyte barcode patterns and additionally at least one second alignment marker; and an image processor that aligns associated images for selected sample retention regions using the at least one first alignment marker and further aligns images for analyte detection regions with corresponding images for selected sample retention regions using the at least one second alignment marker, the image processor further identifying retained at least one cell in respective sample retention regions and corresponding analyte barcode patterns to discretely resolve released analytes associated with the retained at least one cell based on the analyte detection moieties detected in the analyte barcode pattern.

2. The system of claim 1 , wherein the image processor further evaluates the sample retention region images to determine image characteristics for associated sample retention regions.

3. The system of claim 2 , wherein the image processor gates resolution of analytes and cellular associations based on the image characteristics of the sample retention regions.

4. The system of claim 1 , wherein the image processor further evaluates the sample retention region images to determine image characteristics for the retained at least one cell.

5. The system of claim 4 , wherein the system further comprises a cell template database including a plurality of cell images accessed by the image processor to identify the retained at least one cell by comparison of image characteristics with the plurality of cell images.

6. The system of claim 5 , wherein the image processor identifies the retained at least one cell on the basis of similarity of image characteristics with at least one cell image in the cell template database.

7. The system of claim 1 , wherein the at least one cell is labelled with at least one antibody, stain or dye that identifies the presence of at least one surface marker in at least one of the plurality of images is used by the image processor for cellular identification.

8. The system of claim 7 , wherein the at least one labelled cell detected in at least one of the plurality of images is used by the image processor to discriminate between different types of cells.

9. The system of claim 1 , wherein the at least one cell is labelled with a stain or dye detected in at least one of the plurality of images identifies cells as live or dead or highlights metabolic processes of cells.

10. The system of claim 1 , wherein at least two or more discrete regions of the analyte barcode pattern associated with selected at least one cell are evaluated by the image processor to resolve released analytes for the selected at least on cell.

11. The system of claim 1 , wherein the image processor further performs a background intensity determination for an image having at least one selected sample retention region lacking a corresponding retained cell.

12. The system of claim 11 , wherein the image processor compares the determined background intensity to an intensity associated with a region of the analyte barcode pattern associated with selected at least one cell to be evaluated to resolve released analytes for the selected at least one cell.

13. The system of claim 1 , wherein the image processor further identifies sample retention chambers retaining single cells and compares the discretely resolved released analytes for the single cells to reflect a distribution of detected analytes for the population of cells.

14. The system of claim 13 , wherein the distribution of detected analytes for the population of cells characterizes polyfunctional ability of single cells from the population of cells to release multiple analytes.

15. The system of claim 13 , further comprising an analyte response database comprising analyte profiles for patient, therapeutic, or disease response associated with selected analytes wherein the image processor compares the distribution of detected analytes for the population of cells to the analyte response database to correlate detected released analytes in the population of cells with the analyte profiles in the analyte response database.

16. The system of claim 1 , wherein the analytes are selected from the group consisting of biomolecules, organic molecules, inorganic molecules, nucleic acids, peptides, proteins, antibodies, cytokines, chemokines, and ions.

17. The system of claim 1 , wherein the analytes comprise cytokines or proteins secreted by the at least one cell from the population of cells and are selected from the group consisting of CCl-11, GM-CSF, Granzyme B, IFN-γ, IL-10, IL-12, IL-13, IL-17A, IL-17F, IL-18, IL-1β, IL-2, IL-21, IL-22, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IP-10, MCP-1, MCP-4, MIP-1α, MIP-1β, Perforin, RANTES, sCD137, sCD40L, TGF-β1, TNF-α, and TNF-β.

18. The system of claim 1 , wherein the cells are selected from the group consisting of B-cells, T cells, CD4+ cells, CD8+ cells, macrophage cells, dendritic cells, epithelial cells, brain cells, tumor cells, malignant cells and diseased cells.

19. A method for discretely resolving analytes associated with a cellular population comprising: acquiring a plurality of images for a plurality of sample retention regions that receive at least one cell distributed from a population of cells and retain an associated plurality of analytes released by the at least one cell; acquiring a plurality of images for a plurality of analyte detection regions patterned with a plurality of discretely positioned analyte detection moieties, the analyte detection regions disposed along parallel lines forming a barcode pattern alignable with the sample retention regions whereby, upon coupling, released analytes selectively associate with the plurality of analyte detection moieties forming an analyte barcode pattern for each analyte detection region; resolving a plurality of first alignment markers disposed about the plurality of sample retention regions; resolving a plurality of second alignment markers disposed about the plurality of analyte detection regions; aligning associated images for selected sample retention regions using at least one of the plurality of first alignment markers and further aligning images for analyte detection regions with corresponding images for selected sample retention regions using the at least one of the plurality of second alignment markers; and identifying retained at least one cell in respective sample retention regions and corresponding analyte barcode patterns to discretely resolve released analytes associated with the retained at least one cell based on the analyte detection moieties detected in the analyte barcode pattern.

20. One or more non-transitory computer-readable media having computer executable code stored thereon for discretely resolving analytes associated with a cellular population, the code comprising: an executable routine for acquiring a plurality of images for a plurality of sample retention regions that receive at least one cell distributed from a population of cells and retain an associated plurality of analytes released by the at least one cell; an executable routine for acquiring a plurality of images for a plurality of analyte detection regions patterned with a plurality of discretely positioned analyte detection moieties, the analyte detection regions disposed along parallel lines forming a barcode pattern-alignable with the sample retention regions whereby, upon coupling, released analytes selectively associate with the plurality of analyte detection moieties forming an analyte barcode pattern for each analyte detection region; an executable routine for resolving a plurality of first alignment markers disposed about the plurality of sample retention regions; an executable routine for resolving a plurality of second alignment markers disposed about the plurality of analyte detection regions; an executable routine for aligning associated images for selected sample retention regions using at least one of the plurality of first alignment markers and further aligning images for analyte detection regions with corresponding images for selected sample retention regions using the at least one of the plurality of second alignment markers; and an executable routine for identifying retained at least one cell in respective sample retention regions and corresponding analyte barcode patterns to discretely resolve released analytes associated with the retained at least one cell based on the analyte detection moieties detected in the analyte barcode pattern.